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UNIVERSITY OF BUCHAREST
FACULTY OF PHYSICS Guest
2024-11-22 2:01 |
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Conference: Bucharest University Faculty of Physics 2013 Meeting
Section: Biophysics; Medical Physics
Title:
Biophysical properties of myocardial TRPM7 channels and involvement in pathology
Authors:
Bogdan Amuzescu (1), Bogdan Istrate (1), Asfree Gwanyanya (2), Regina Macianskiene (3), Kanigula Mubagwa (4)
Affiliation:
(1)Dept. Biophysics & Physiology, Faculty of Biology, University of Bucharest, RO 005095, Romania
(2) Dept. Human Biology, University of Cape Town, Cape Town, South Africa
3- Laboratory of Membrane Biophysics, Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania
4- Dept. Cardiovascular Diseases, Faculty of Medicine, Katholieke Universiteit Leuven,
3000 Leuven, Belgium
E-mail
bogdan@biologie.kappa.ro
Keywords:
TRPM7, electrophysiology, patch-clamp, immunofluorescence, myocardial ischemia
Abstract:
TRPM7 is an ubiquitously expressed ion channel, belonging to the melastatin-related group of the transient receptor potential (TRP) superfamily, putatively involved in intracellular magnesium homeostasis and transport of transitional metal ions (iron, copper, zinc, etc.). Along with TRPM6, present mainly in intestinal and renal epithelia, where it plays an important role in magnesium transport, they form a peculiar category of channel-enzymes, featuring a functional alpha-kinase and phosphorylation sites in the C-terminal domain. Our studies led to the identification in ventricular myocytes of different species of a non-selective channel current with permeation and regulation properties virtually identical to TRPM7 in heterologous expression systems. The channel is blocked by trivalent lanthanides, has a particular current-voltage relation, requires ATP and PIP2 for activation, and is inhibited by intracellular magnesium and acidification. Recently we have identified in human atrial myocytes a current with similar permeation, block and regulation properties. In ~1/3 of patients the current was already activated at patch rupture. Our recent immunofluorescence experiments have confirmed the presence of TRPM7 in ventricular cardiomyocytes, showing a preferential location at the Z membranes of the sarcomeres and intercalated disks, and also a peri- and paranuclear staining suggestive for the rough endoplasmic reticulum and Golgi apparatus. Although earlier studies have convincingly demonstrated TRPM7 activation by free oxygen radicals during prolonged neuronal ischemia (Aarts et al. 2003 Cell 115:863-877), and an antiapoptotic effect of nerve growth factor on hippocampal neurons via downregulation of TRPM7 expression, the relevance of TRPM7 activation during myocardial ischemia is currently not understood.
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